Comparative Effectiveness of Therapies for Clinically Localized Prostate Cancer
Executive Summary published 5 Feb 2008 of the U.S. Department of Health & Human Services, www.hhs.gov
cancer is the most common non-dermatologic cancer in men. In 2007 an estimated 218,890 men were diagnosed with, and 27,050
deaths were attributed to, prostate cancer in the United States. Approximately
90 percent of men with prostate cancer have disease considered confined to the prostate gland (clinically localized disease).* Reported prostate cancer incidence has increased with introduction of the prostate-specific
antigen (PSA) blood test. Disease-specific mortality rates have declined, and an estimated 1.8 million men living in the United States have a diagnosis of prostate cancer.
detected prostate cancer is primarily a disease of elderly men. Prostate cancer frequently has a relatively protracted course
even if left untreated, and many men die with, rather than from, prostate cancer. Largely because of widespread PSA testing,
the lifetime risk of being detected with prostate cancer in the United States has nearly doubled to 20 percent.
However, the risk of dying of prostate cancer has remained at approximately 3 percent1. Therefore, considerable over-detection and treatment may exist.
primary goal of treatment is to target the men most likely to need intervention in order to prevent prostate cancer death
and disability while minimizing intervention-related complications. Common treatments include watchful waiting (active surveillance),
surgery to remove the prostate gland (radical prostatectomy), external beam radiotherapy (EBRT) and interstitial radiotherapy
(brachytherapy), freezing the prostate (cryotherapy), and androgen deprivation therapy (ADT). (Treatment options are outlined
in Table A.) All treatments have risks of complications, although frequency and severity may vary. Patient treatment decision-making
incorporates physician recommendations and estimated likelihood of cancer progression without treatment, as well as treatment-related
convenience, costs, and potential for eradication and adverse effects (AEs). Patient characteristics, including race/ethnicity,
age, and comorbidities, have an important role in predicting mortality; the likelihood of treatment-related urinary, bowel,
and sexual dysfunction; treatment tradeoff preferences; and selection. However, little is known about how these characteristics
modify the effect of treatment.
Table A. Treatment options
for clinically localized prostate cancer
Radical retropubic or perineal
Complete surgical removal
of prostate gland with seminal vesicles, ampulla of vas, and sometimes pelvic lymph nodes. Sometimes done laparoscopically
or with robotic assistance and attempt to preserve nerves for erectile function.
External beam radiotherapy
Multiple doses of radiation
from an external source applied over several weeks. Dose and physical characteristics of beam may vary. Conformal radiotherapy
uses 3D planning systems to maximize dose to prostate cancer and attempt to spare normal tissue.
radiation therapy (IMRT) provides the precise adjusted dose of radiation to target organs, with less irradiation of healthy
tissues than conformal radiation therapy.
Proton radiation therapy is a form of EBRT in which protons rather than
photons are directed in a conformal fashion to a tumor site. The use of the heavier single proton beam (vs. photon therapy)
allows for a low entrance dose and maximal dose at the desired tumor location with no exit dose. This theoretically permits
improved dose distribution (delivering higher dose to the tumor with lower dose to normal tissue) than other EBRT techniques.
May be used alone or in combination with proton and photon-beam radiation therapy.
Radioactive implants placed
under anesthesia using radiologic guidance. Lower dose/permanent implants typically used. External beam "boost" radiotherapy
and/or androgen deprivation sometimes recommended.
Destruction of cells through
rapid freezing and thawing using transrectal guided placement of probes and injection of freezing/thawing gases.
Androgen deprivation therapy
Oral or injection medications
or surgical removal of testicles to lower or block circulating androgens.
Watchful waiting (active
Active plan to postpone
intervention. May involve monitoring with digital rectal exam/prostate-specific antigen test and repeat prostate biopsy with
further therapy (either curative or palliative) based on patient preference, symptoms, and/or clinical findings.
Laparoscopic radical prostatectomy
(LRP) and robotic assisted radical prostatectomy (RLRP)
invasive surgical method to remove the prostate.
High-intensity focused ultrasound
High-intensity focused ultrasound
therapy has been used as a primary therapy in patients with localized prostate cancer not suitable for radical prostatectomy.
Tissue ablation of the prostate is achieved by intense heat focused on the identified cancerous area.
to the advent of widespread PSA testing, most prostate cancers were detected based on abnormalities on the digital rectal
examination (DRE) or incidentally from tissue obtained at surgery for treatment of symptoms due to benign prostatic obstruction.
The vast majority of prostate cancers currently detected in the United States are asymptomatic, clinically localized, and found on routine PSA testing. PSA testing detects more tumors, at an earlier
stage, with smaller volume within each stage, and at an earlier period in a man’s life than non-screen-detected tumors.
The clinical significance, natural history, and comparative effectiveness of treatments in PSA-detected cancers are not known
but likely differ from those detected and treated in the pre-PSA era (before the late 1980s to early 1990s).
primary measure of tumor aggressiveness is the Gleason histologic score, although efforts are underway to identify more reliable
prognostic factors. A classification currently recommended incorporates PSA levels, Gleason histologic score, and tumor volume
to identify low-, intermediate-, and high-risk tumors based on their likelihood of progressing with no treatment as well as
recurring (or failing to be eradicated) following early intervention. In addition to patient and provider factors, it is important
to determine how tumor characteristics (e.g., Gleason score, tumor volume, screen vs. clinically detected tumors) affect the
outcomes of interventions.
and hospital characteristics may affect treatment selection and outcomes. The effect of provider volumes on clinical outcomes
in men with localized prostate cancer is not well established. Specialty and geographical location of providers influence
diagnostic strategies and the management of localized prostate cancer. Variability in the management of localized prostate
cancer is often based on physician opinions and specialty. Diagnosis of localized disease is based primarily on a screening
of asymptomatic patients. Therefore, differences in screening practices may be associated with differences in the stage of
tumors detected and recommendations for intervention. Physician recommendations play an important role in patient decisions
on treatment preferences. Recent studies showed that patient and physician treatment preferences reflect perceived personal
factors more than evidence-based recommendations.
report summarizes evidence comparing the relative effectiveness and safety of treatment options for clinically localized prostate
cancer. The report addresses the following questions:
1. What are the comparative risks, benefits, short- and long-term outcomes of therapies for clinically
localized prostate cancer?
2. How do specific patient characteristics, e.g., age, race/ethnicity, presence or absence of comorbid
illness, preferences (e.g., tradeoff of treatment-related adverse effects vs. potential for disease progression), affect the
outcomes of these therapies, overall and differentially?
3. How do provider/hospital characteristics affect outcomes overall and differentially (e.g., geographic
region and volume)?
4. How do tumor characteristics, e.g., Gleason score, tumor volume, screen vs. clinically detected
tumors, affect the outcomes of these therapies, overall and differentially?
findings covered in this report are summarized in Table B.
Key Question 1. What are the comparative risks, benefits, and outcomes of therapies?
one therapy can be considered the preferred treatment for localized prostate cancer due to limitations in the body of evidence
as well as the likely tradeoffs an individual patient must make between estimated treatment effectiveness, necessity, and
adverse effects. All treatment options result in adverse effects (primarily urinary, bowel, and sexual), although the severity
and frequency may vary between treatments. Even if differences in therapeutic effectiveness exist, differences in adverse
effects, convenience, and costs are likely to be important factors in individual patient decision-making. Patient satisfaction
with therapy is high and associated with several clinically relevant outcome measures. Data from nonrandomized trials are
inadequate to reliably assess comparative effectiveness and adverse effects. Additional randomized controlled trials (RCTs)
Limitations in the existing evidence include the following:
Few randomized trials directly
compared the relative effectiveness between (rather than within) major treatment categories.
Many randomized trials are inadequately
powered to provide long-term survival outcomes, with the majority reporting biochemical progression or recurrence as the main
Some randomized trials were old,
conducted prior to prostate cancer detection with PSA testing (i.e., studies before the current era, when tumors are diagnosed
in an earlier stage, giving more lead time, and there is a higher percentage of benign tumors, resulting in length bias and
over-diagnosis), and used technical aspects of treatment that may not reflect current practice; therefore, their results may
not be generalizable to modern practice settings.
Wide variation existed in reporting
and definitions of outcomes.
There was little reporting of outcomes
according to major patient and tumor characteristics.
Emerging technologies have not
been evaluated in randomized trials.
Randomized comparisons across primary treatment categories
Radical prostatectomy compared
with watchful waiting (2 RCTs). Compared
with men who used watchful waiting (WW), men with clinically localized prostate cancer detected by methods other than PSA
testing and treated with radical prostatectomy (RP) experienced fewer deaths from prostate cancer, marginally fewer deaths
from any cause, and fewer distant metastases. The greater benefit of RP on cancer-specific and overall mortality appears to
be limited to men under 65 years of age but is not dependent on baseline PSA level or histologic grade. Two RCTs compared
WW with RP. The Scandinavian Prostate Cancer Group (SPCG) trial found significantly lower incidences of all-cause deaths (24
vs. 30 percent), disease-specific deaths (10 vs. 15 percent), and distant metastases (14 vs. 23 percent) for subjects treated
with RP than for subjects assigned WW after a median follow-up of 8.2 years. Surgery was associated with greater urinary and
sexual dysfunction than WW. An older trial of 142 men found no significant differences in overall survival between RP and
WW after a median follow-up of 23 years, although small sample size limited study power.
Radical prostatectomy vs. external
beam radiotherapy (1 RCT). One small (N=106),
older trial indicated that, compared with EBRT, RP was more effective in preventing progression, recurrence, or distant metastases
in men with clinically localized prostate cancer detected by methods other then PSA testing. Treatment failure at 5 years
of follow-up, defined as acid phosphatase elevation on two consecutive follow-up visits or appearance of bone or parenchymal
disease with or without concomitant acid phosphatase elevation, occurred in 39 percent for EBRT compared with 14 percent for
Cryotherapy, laparoscopic or
robotic assisted radical prostatectomy, primary androgen deprivation therapy, high-intensity focused ultrasound (HIFU), proton
beam radiation therapy, or intensity modulated radiation therapy (IMRT) (0 RCTs). It is not known whether these therapies are better or worse than other treatments
for localized prostate cancer because these options have not been evaluated in RCTs.
Randomized comparisons within primary treatment categories
Radical prostatectomy combined
with neo-adjuvant androgen deprivation therapy (5 RCTs). The addition of neo-adjuvant hormonal therapy to RP did not improve survival or cancer recurrence rates, defined by
PSA recurrence, but increased AEs. One small RCT comparing RP alone and RP combined with neo-adjuvant ADT found no overall
or disease-specific survival benefit with the addition of neo-adjuvant ADT after a median follow-up of 6 years. The addition
of neo=adjuvant ADT did not prevent biochemical progression compared with RP alone in any of the four trials. The trial comparing
3 months and 8 months neo-adjuvant ADT with RP reported greater AEs in the 8-month group than the 3-month group (4.5 percent
vs. 2.9 percent) and higher incidence of hot flashes (87 percent vs. 72 percent).
External beam radiotherapy:
comparison of EBRT regimens (5 RCTs). No
RCTs compared EBRT and WW. It is not known if using higher doses of EBRT by increasing either the total amount or type of
radiation (e.g., via high-dose intensity modulated or proton beam or by adding brachytherapy) improves overall or disease-specific
survival compared with other therapies. No EBRT regimen, whether conventional, high-dose conformal, dose fractionation, or
hypofractionation, was superior in reducing overall or disease-specific mortality. Increasing the total amount of radiation
or adding brachytherapy after EBRT decreased cancer recurrence compared with lower doses of radiation. One trial (N=936) found
that the probability of biochemical or clinical progression at 5 years was lower in the long-arm group (66 Gy in 33 fractions)
than the short-arm group (52.5 Gy in 20 fractions). Conventional-dose EBRT (64 Gy in 32 fractions) and hypofractionated EBRT
(55 Gy in 20 fractions) resulted in similar PSA relapse. One trial (N=104) found that brachytherapy combined with EBRT reduced
biochemical or clinical progression compared with EBRT alone. One trial (N=303) found that high-dose EBRT (79.2 Gy that included
3D conformal proton 50.4 Gy with 28.8 Gy proton boost) was more effective than conventional-dose EBRT (70 Gy that included
19.8 Gy proton boost) in the percentage of men free from biochemical failure at 5 years (80 percent in the high-dose group
and 61 percent in the conventional-dose group). Effectiveness was evident in low-risk disease (PSA <10 ng/ml, stage ≤T2a
tumors, or ≤Gleason 6) and higher risk disease. Acute combined gastrointestinal (GI) and genitourinary (GU) toxicity
was lower in the long arm (7.0 percent) than in the short arm (11.4 percent). Late toxicity was similar. There were no significant
differences between conventional and hypofractionated EBRT with the exception of rectal bleeding at 2 years after therapy,
which had a higher prevalence in the hypofractionated group. Acute GI or GU symptoms of at least moderate severity were similar
in the trial comparing high and conventional doses.
External beam radiotherapy combined
with androgen deprivation therapy compared with EBRT alone (3 RCTs). ADT combined with EBRT (ADT + EBRT) may decrease overall and disease-specific mortality but increase
AEs compared with EBRT alone in high-risk patients defined by PSA levels and Gleason histologic score (PSA >10 ng/ml or
Gleason >6). One RCT (N=216) found that conformal EBRT combined with 6 months of ADT reduced all-cause mortality, disease-specific
mortality, and PSA failure compared with conformal EBRT alone after a median follow-up of 4.5 years. There were significant
increases in gynecomastia and impotence in the ADT + EBRT group compared with EBRT alone. One RCT (N=206) found that 6 months
of ADT + EBRT did not significantly reduce disease-specific mortality compared with conformal EBRT alone in T2b and T2c subjects
after a median follow-up of 5.9 years. Six months of combination therapy reduced clinical failure, biochemical failure, or
death from any cause compared with EBRT alone in subjects with T2c disease but not in T2b subjects.
Different doses of adjuvant
external beam radiotherapy combined with brachytherapy (1 RCT). One small trial comparing different doses of supplemental EBRT, 20 Gy (N=83) vs. 44 Gy (N=76), adjuvant
to brachytherapy (103Pd) implant found no significant differences in the number of biochemical failure events and
freedom from biochemical progression at 3 years.
Brachytherapy compared with
brachytherapy (1 RCT). No RCTs compared brachytherapy
alone with other major treatment options. Preliminary results from one small trial (N=126) comparing 125I with
103Pd brachytherapy found similar biochemical control at 3 years. There was a trend toward more radiation proctitis,
defined as persistent bleeding, with 125I.
Adjuvant with standard care:
RP, EBRT, or WW (3 RCTs). Androgen deprivation
with bicalutamide alone or in addition to RP or EBRT did not reduce cancer recurrence or mortality. There was no difference
in total number of deaths between the bicalutamide and placebo groups for men receiving RP or EBRT at the median follow-up
of 5.4 years. Among WW subjects, there were significantly more deaths with bicalutamide compared with placebo. The addition
of bicalutamide to standard care did not reduce progression.
outcomes data from nonrandomized reports
supplement RCT findings and summarize the literature on treatment for localized prostate cancer, we used the database of the
Clinical Guideline Panel for Treatment of Clinically Localized Prostate Cancer of the American Urological Association. This
work relied on data extracted from 436 articles published between 1991 and April 2004 on T1-T2 prostate cancer. Over 80 percent
were case series and only 6 percent were controlled trials. Data interpretation is limited by variability in result reporting,
lack of controls, and likelihood that the database contained results from multiple publications using identical or nearly
identical populations. Overall and disease-specific mortality were infrequently reported. When reported, there was extremely
wide variation within and between treatments, making overall estimates of outcomes difficult. There was not standardized reporting
of biochemical outcomes, with more than 200 definitions of “biochemical no evidence of disease (bNED)” reported.
Results demonstrated extremely wide and overlapping ranges of outcomes at 5 and 10 years within and between treatments.
effects were reported, but definitions and severity varied widely. It was not possible to provide precise estimates regarding
comparative effectiveness or specific AEs for each treatment option. Urinary dysfunction appeared to be more common in men
treated with RP than in men treated with EBRT. Sexual dysfunction was common following all treatments. Impotence rates ranged
from less than 5 percent to approximately 60 percent in the few studies reporting on men undergoing nerve-sparing RP.
estimates for U.S. population-based AEs at 5 years following treatment were obtained from a large
survey of Medicare-eligible men who had undergone treatment for localized prostate cancer. Urinary dysfunction, defined as
no control or frequent leaking of urine, occurred in 14 percent of men undergoing RP and 5 percent undergoing EBRT. Use of
pads to stay dry was greater after RP (29 percent) than EBRT (4 percent). Bowel dysfunction was lower in men receiving RP
than EBRT, although the only significant difference was related to bowel urgency (18 percent vs. 33 percent). Erection insufficient
for intercourse occurred in approximately three-quarters of men regardless of treatment. When adjusting for baseline factors,
erectile dysfunction (ED) was greater with RP (odds ratio=2.5, 95-percent confidence interval=1.6, 3.8).
Cryosurgery. No randomized trials evaluated cryosurgery, and the majority of reports included
patients with T3-T4 stages. Overall or prostate-cancer-specific survival was not reported. Progression-free survival in patients
with T1-T2 stages ranged from 29 to 100 percent. AEs were often not reported but, when described, included bladder outlet
obstruction (3 to 21 percent), tissue sloughing (4 to 15 percent), and impotence (40 to 100 percent). Outcomes may be biased
by patient and provider characteristics.
and robotic assisted prostatectomy. Three reviews estimated
the effectiveness and AEs of laparoscopic and robotic assisted prostatectomy from 21 nonrandomized trials and case series.
Most originated from centers outside of the United States. Median follow-up
was 8 months. Laparoscopic RP had longer operative time but lower blood loss and improved wound healing compared with open
retropubic RP. Reintervention rates were similar. Results from eight nonrandomized reports suggested that total complications,
continence rates, positive surgical margins, and operative time were similar for robotic assisted and open RP. Median length
of hospital stay (1.2 vs. 2.7 days) and median length of catheterization (7 vs. 13 days) were shorter after robotic assisted
RP than open RP.
modulated radiation therapy. There was no direct evidence that
IMRT results in better survival or disease-free survival than other therapies for localized prostate cancer. Based on nonrandomized
data, the absolute risks of clinical and biochemical outcomes (including tumor recurrence), toxicity, and quality of life
after IMRT are comparable with conformal radiation. There is low-level evidence that IMRT provides at least as good a radiation
dose to the prostate with less radiation to the surrounding tissues compared with conformal radiation therapy.
EBRT. There were no data from randomized trials comparing EBRT
using protons vs. conventional EBRT or other primary treatment options. In one randomized trial, men with localized prostate
cancer had statistically significantly lower odds of biochemical failure (increase in PSA) 5 years after the higher dose of
EBRT with a combination of conformal photon and proton beams without increased risk of adverse effects. Based on nonrandomized
reports, the rates of clinical outcomes and toxicity after proton therapy may be comparable with conformal radiation. There
was no direct evidence that proton EBRT results in better overall or disease-free survival than other therapies.
focused ultrasound therapy. There were no data from randomized
trials comparing HIFU with other primary treatment options. Biochemical progression-free survival rates of 66 to 87 percent
and negative biopsy rates of 66 to 93 percent were reported from non-controlled studies. The absolute risk of impotence and
treatment-related morbidity appeared to be similar to other treatments. Follow-up duration was <10 years.
status, quality of life, and treatment satisfaction. Eight studies
of health status and quality of life, including a U.S. population-based survey,
were eligible. Bother due to dripping or leaking of urine was more than six-fold greater in RP-treated men than in men treated
with EBRT after adjusting for baseline factors. Bother due to bowel dysfunction (4 vs. 5 percent) or sexual dysfunction (47
vs. 42 percent) was similar for RP and EBRT. In a subgroup of men ages 70 and over, bother due to urine, bowel, or sexual
dysfunction was 5.1, 2.4, and 2.8 times higher, respectively, for aggressive (RP/EBRT) vs. conservative (WW/ADT) therapy.
Satisfaction with treatment was high, with less than 5 percent reporting dissatisfaction, unhappiness, or feeling terrible
about their treatment, although the highest percent was among those treated with RP. Treatment satisfaction was highly correlated
with bowel, bladder, and erectile function; general health status; belief that the respondent was free of prostate cancer;
and whether cancer treatments limited activity or relationships. More than 90 percent said they would make the same treatment
decision again, regardless of treatment received.
Key Question 2. How do patient characteristics affect outcomes?
RCTs reported head-to-head comparisons of treatment outcomes stratified by race/ethnicity, and most did not provide baseline
racial characteristics. Available data were largely from case series. Few studies reported head-to-head comparisons, and there
was limited adjustment for confounding factors. Modest treatment differences reported in some nonrandomized studies have not
been consistently reported in well-powered studies. There was little evidence of a differential effect of treatments based
on age. While differences exist in the incidence and morbidity of prostate cancer based on patient age and there are differences
in the treatments offered to men at different age ranges, few studies directly compared the treatment effects of different
therapies across age groups. Most RCTs did not have age exclusion criteria. The mean/median age ranged from a low of 63 years
for trials of RP to 72 years for trials of EBRT. Only one RCT provided subgroup analysis according to age. Results suggest
that survival benefits of RP compared with WW may be limited to men under 65 years of age. Practice patterns from observational
studies show that RP is the most common treatment option in younger men with localized prostate cancer.
Key Question 3. How do provider and hospital characteristics affect outcomes?
from national administrative databases and surveys suggested that provider/hospital characteristics, including RP procedure
volume, physician specialty, and geographic region, affect outcomes. (There was no information on volume and outcomes for
brachytherapy, cryotherapy, or EBRT.) Patient outcomes varied in different locations and were associated with provider and
hospital volume independent of patient and disease characteristics. Screening practices can influence the characteristics
of patients diagnosed and tumors detected. Screening practices and treatment choices varied by physician specialty and across
regions of the United States. These did not correlate with clinician availability. Clinicians were more likely
to recommend procedures they performed regardless of tumor grades and PSA levels.
variation existed in physician availability, ratio of urologists and radiation oncologists per 100,000 adult citizens based
on surveys conducted by the American Medical Association, screening practice, incidence, mortality, and treatment selection.
The direction of regional variation was not always consistent. Several studies reported geographic variation at the county,
State, or U.S. Census region level. Overall, many different methods were used to report geographic variation, so pooling of
results was difficult; when results were pooled, the geographic regions used were quite large.
RP volume was not associated with RP-related mortality and positive surgical margins. However, the relative risk of surgery-related
complications adjusted for patient age, race, and comorbidity and for hospital type and location was lower in patients treated
by higher volume surgeons. Urinary complications and incontinence were lower for patients whose surgeons performed more than
40 RPs per year. The length of hospital stay was shorter in patients operated on by surgeons who performed more RPs per year.
Cost was not associated with surgeon volume. Surgeon volume of robotic laparoscopic RP was marginally associated with lower
adjusted odds of extensive (but not any or focal) positive margins.
volume and teaching status were associated with patient outcomes. Despite different definitions of “high” and
“low” hospital volumes in individual studies, pooled analysis showed that surgery-related mortality and late urinary
complications were lower and length of stay was shorter in hospitals that performed more RPs per year. Hospital readmission
rates were lower in hospitals with greater volume. Teaching hospitals had a lower rate of surgery-related complications and
higher scores of operative quality. Several studies found differences in treatment and outcome based on whether the patient
was seen in an HMO (health maintenance organization) or fee-for-service organization and whether the patient was a Medicare
beneficiary. Variability in the use of ADT was more attributable to individual differences among urologists than tumor or
Key Question 4. How do tumor characteristics affect outcomes?
data existed on the comparative effectiveness of treatments based on PSA levels, histologic score, and tumor volume to identify
low-, intermediate-, and high-risk tumors. We focused on baseline PSA levels and Gleason histologic score. The natural history
of PSA-detected tumors is not known because few men remain untreated for a long period. One report assessed 20-year outcomes
in the United States from a cohort of 767 men with prostate cancer detected prior to PSA testing
and treated with WW. Histologic grade was associated with overall and prostate-cancer-specific survival. Men with low-grade
prostate cancers had a minimal risk of dying from prostate cancer (7 percent with Gleason score 2-4 died due to prostate cancer).
Men with high-grade prostate cancers had a high probability of dying from their disease within 10 years of diagnosis, regardless
of their age at diagnosis (53 percent with Gleason score 8-10 died due to prostate cancer). Estimates from large ongoing screening
trials suggest that PSA increases the time of detection by 5-15 years. Therefore, it is likely that men with PSA-detected
tumors will have better 20-year disease-specific survival than this cohort.
RCTs did not exclude participants based on PSA levels or tumor histology, and few provided comparative analysis according
to these factors. Secondary analysis of one randomized trial concluded that disease-specific mortality at 10 years for men
having RP compared with WW differed according to age but not baseline PSA level or Gleason score. Men with Gleason scores
8-10 were more likely to have evidence of biochemical recurrence than men with Gleason scores 2-6, regardless of whether treatment
was RP alone or RP combined with neo-adjuvant hormonal therapy (NHT). High-dose EBRT was more effective in controlling biochemical
failure than conventional dose therapy in both low-risk disease (PSA <10 ng/ml, stage ≤T2a tumors, or Gleason ≤6)
and higher risk disease. When the higher risk subjects were further divided into intermediate risk and high-risk groups, the
benefit of high-dose therapy remained for the intermediate-risk but not for the high-risk patients.
on very limited nonrandomized trial data, disease-specific survival was similar for men treated with EBRT or with RP in men
with baseline PSA >10 ng/ml. Men with Gleason scores 8-10 were more likely to have biochemical recurrence than men with
Gleason scores 2-6, regardless of type of treatment
Uncertainty about the comparative effectiveness and harms of the primary treatments for localized prostate cancer is
the major gap in knowledge. This is mainly due to the paucity of direct head-to-head RCTs and the excess reliance on nonrandomized
data to compare the most common treatment options: WW, RP, EBRT, brachytherapy, and ADT. Emerging technologies such as IMRT,
proton beam radiation, laparoscopic and robotic assisted prostatectomy, and cryotherapy are increasingly being used despite
the absence of long-term comparative RCTs.
Initiation and completion of long-term, adequately powered randomized trials (particularly comparative trials across,
rather than within, primary treatment modalities) are needed. Where randomized trials have been conducted, confirmation (or
refutation) of findings with additional randomized trials is needed because evidence is often based on results from a single
relatively small study. These trials should standardize reporting of key clinically relevant outcomes, including overall,
disease-specific, and metastatic-free survival; bNED; adverse effects; and disease-specific quality of life/health status.
Ideally, relative effectiveness and adverse effects would be stratified according to tumor (PSA, stage, histologic grade)
and patient (age, race, comorbidity) characteristics. A previous RCT comparing RP and brachytherapy was discontinued due to
inadequate recruitment. However, several trials are ongoing, including comparisons of RP vs. WW, RP vs. EBRT or WW, cryotherapy
vs. EBRT, and active surveillance with delayed intervention vs. early intervention with RP. Results will not be available
for several years. Patients and their support groups, clinicians, researchers, and funders need to ensure successful initiation
High-quality, large prospective cohort studies or cancer registries that identify men at the time of diagnosis and
proceed to collect comprehensive patient, tumor, and treatment decision selection characteristics could help target future
RCTs to the most promising research questions. These may be able to provide information related to important patient characteristics
(age, race, comorbidities) or tumor characteristics (PSA, stage, histologic grade) that may not be adequately addressed in
RCTs currently in progress due to sample size limitations. Nonrandomized studies should report head-to-head comparisons, adjust
for confounding factors, and use standardized definitions of disease-specific and biochemical survival, adverse effects, and
Identification of biomarkers to provide reliable estimates about prostate cancer aggressiveness and the relative effectiveness
of treatments is needed. This would reduce unnecessary interventions while focusing treatment on men most likely to benefit.
A new generation of educational materials is required to provide balanced information about the risks and benefits of treatments
and assist in patient decision-making and incorporation of patient-centric values (tumor eradication, impact of AEs, anxiety,
costs, convenience, etc.). It is hoped that these materials incorporate findings from comprehensive systematic reviews that
use methods to limit bias and assess quality of evidence. The resulting patient and provider guides can be developed to summarize
these findings in a format that is understandable and useful for consumers. Structure and process measures are associated
with quality of prostate cancer care. Research across nationally representative databases using methods of risk adjustment
is needed to clarify geographical differences in patient outcomes. Identification of factors associated with outcomes and
development of system wide methods for implementation or improvement are needed.
executive summary is part of the following document: Wilt TJ, Shamliyan T, Taylor B, MacDonald R, Tacklind J, Rutks I, Koeneman
K, Cho C-S, Kane RL. Comparative Effectiveness of Therapies for Clinically Localized Prostate Cancer. Comparative Effectiveness
Review No. 13. (Prepared by Minnesota Evidence-based Practice Center under
Contract No. 290-02-00009.) Rockville, MD: Agency for Healthcare Research and Quality. February 2008. Available at: effectivehealthcare.ahrq.gov/healthInfo.cfm.
For print copies of Comparative Effectiveness of Therapies for Clinically Localized Prostate Cancer: Executive Summary
No. 13 (AHRQ Pub. No. 08-EHC010-1), please call the AHRQ Clearinghouse at 1-800-358-9295.
1 The reasonable interpretation of
such small (3% lower risk of dying of prostate cancer) decline forces the conclusion that the more active surveillance along
with more of those in stage 3 & 4 have favorable outcomes due to an early detection due to the PSA. The change is not because of treatment, but in spite of it, since the best course is the traditional surgical
intervention, and the newer, non-invasive interventions actually have a worse outcome—a fact acknowledge by Urology,
7th Edition. Claims otherwise, it states are based on different endpoints in
About 90% of those diagnosed have a Gleason score of 1 or 2, and have
only a 4-7% chance of dieing of prostate cancer within the next 15 years—only moderately above the rate for the general
population in their age group. A low score indicates that the cells are only
in appearance slightly abnormal; a high score (6 or 7) indicates that the cells are much more likely to become invasive. The method of diagnosis (microscopy) can distinguish a small clump of non-invasive cells with a low Gleason score from a small
clump of similar-appearing invasive cells. Both clumps are labeled as andrenocarcinoma. The non-invasive (low gleason score) cells to become invasive typically must have
one more mutation, such as the one that permits the growth of capularies. Without this mutation the cancerous cells will not have enough oxygen and nutrients
to invade other tissues. Another essential mutation is one which permits metastases.
Cells with a high Gleason score are statistically more likely to have both of these essential mutations, there the similar
more-normal appearing cells. Calling
these near normal in appearance cells andrenocarcinoma is great for business, but
has only a small impact upon the mortality o